We propose to evaluate, prospectively, the impact of moderate daily alcohol consumption, regular weekly patterns of consumption, and usual percent of alcohol consumed with meals, on risk of diabetes mellitus, hypertension, cardiovascular disease and total mortality in large cohort studies of 51,529 middle-aged men who were 40 to 75 years of age at baseline in 1986 (Health Professionals Follow-up Study), and 116,601 young women who were 25 to 42 years of age at baseline in 1989 (Nurses' Health Study II). In addition, using samples (n=500 men and 500 women) of stored plasma from 18,018 men who provided blood specimens in 1993-94 and from an anticipated 40,000 women who will provede blood samples in 1995-96, we propose to evaluate the impact of moderate alcohol consumption on plasma lipids and thrombotic factors related to risk of coronary heart disease. Using a cross-sectional design we propose to evaluate the relationship between alcohol consumption patterns and levels of plasma HDL-cholesterol, tissue-type plasminogen activator (t-PA), fibrinogen, factor VII activity, and von Willebrand Factor independent of obesity, physical activity, and dietary intake of saturated fac, cholesterol, and total energy. Finally, in a nested case-control study of CHD, we propose to evaluate simultaneously the relationship between alcohol consumption patterns, biomarkers, and risk of coronary heart disease to quantitate the importanceof each biomarker in explaining the reported inverse association between alcohol consumption and risk of coronary heart disease. The ongoing HPFS (CA55075 HL35464) and NHS II (CA50385) will provide follow-up and documentation of hypertension, cardiovascular disease, and mortality in addition tocovariate information. Overall, the large size of these cohorts, the prospective design, the high follow-up rates, the detailed alcohol data, and the availability of archived blood specimens provide a unique opportunity to test a number of hypotheses of public health importance, using a highly cost-effective design.